The pluripotency of ES cells, combined with their ease of genetic manipulation and selection, has revolutionized gene functional studies in vivo via the generation of transgenic, chimeric and knockout mice. New technologies are evolving that will make the ability to perform appropriate manipulations of ES cells even more important for the next generation of mouse mutants (Draper and Nagy, 2007). These include, for example, the combination of inducible recombinases (Cre and Flp) for regulated temporal and spatial ablation of genes, RNAi, and development of new techniques that accelerate generation of completely ES cell derived FO mice (i.e. tetraploid aggregation and laser-assisted injection). The main service of Core 4 is to provide to NINDS-funded Qualifying Investigators a high level of expertise in mouse ES cell targeting in order to permit the efficient generation of animal models for neurobiological research. In addition to ES cell electroporation and characterization, the staff of the Core 4 will work with the NINDS-funded investigators to establish and characterize ES cell lines from a number of genetic backgrounds (particularly C57BI/6) that allow mice to be generated on a pure genetic background. Finally, Core 4 will maintain a bank of genetically marked ES cell lines. The ES cells and mice generated from these lines will be used for in vivo lineage tracing and in vitro differentiation into neuronal and glial cell lines.